By multiplexing information symbols in the delay-Doppler(DD)domain,orthogonal time frequency space(OTFS)is a promising candidate for future wireless communication in high-mobility scenarios.In addition to the superior...By multiplexing information symbols in the delay-Doppler(DD)domain,orthogonal time frequency space(OTFS)is a promising candidate for future wireless communication in high-mobility scenarios.In addition to the superior communication performance,OTFS is also a natural choice for radar sensing since the primary parameters(range and velocity of targets)in radar signal processing can be inferred directly from the delay and Doppler shifts.Though there are several works on OTFS radar sensing,most of them consider the integer parameter estimation only,while the delay and Doppler shifts are usually fractional in the real world.In this paper,we propose a two-step method to estimate the fractional delay and Doppler shifts.We first perform the two-dimensional(2D)correlation between the received and transmitted DD domain symbols to obtain the integer parts of the parameters.Then a difference-based method is implemented to estimate the fractional parts of delay and Doppler indices.Meanwhile,we implement a target detection method based on a generalized likelihood ratio test since the number of potential targets in the sensing scenario is usually unknown.The simulation results show that the proposed method can obtain the delay and Doppler shifts accurately and get the number of sensing targets with a high detection probability.展开更多
While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a f...While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.展开更多
Hepatocellular carcinoma(HCC)is the global leading cause of cancer-related deaths due to the deficiency of targets for precision therapy.A new modality of epigenetic regulation has emerged involving RNA-RNA crosstalk ...Hepatocellular carcinoma(HCC)is the global leading cause of cancer-related deaths due to the deficiency of targets for precision therapy.A new modality of epigenetic regulation has emerged involving RNA-RNA crosstalk networks where two or more competing endogenous RNAs(ceRNAs)bind to the same microRNAs.However,the contribution of such mechanisms in HCC has not been well studied.Herein,potential HMGB1-driven RNA-RNA crosstalk networks were evaluated at different HCC stages,identifying the mT0RC2 component RICTOR as a potential HMGB1 ceRNA in HBV^(+)early stage HCC.Indeed,elevated HMGB1 mRNA was found to promote the expressio n of RICTOR mRNA through competitively bin ding with the miR-200 family,especially miR-429.Functio nal assays emplo ying overexpressi on or in terference strategies dem on strated that the HMGB1 and RICTOR 3zuntra nslated regions(UTR)epigenetically promoted the malignant proliferation,self-renewal,and tumorigenesis in HCC cells.Intriguingly,in terference agai nst HMGB1 and RICTOR in HCC cells promoted a stron ger an ti-PD-L1 immuno therapy resp on se,which appeared to associate with the production of PD-L1^(+)exosomes.Mechanistically,the HMGB1-driven RNA-RNA crosstalk network facilitated HCC cell glutamine metabolism via dual mechanisms,activating a positive feedback loop involving mT0RC2-AKT-C-MYC to upregulate glutamine synthetase(GS)expression,and inducing mTORCI signaling to derepress SIRT4 on glutamate dehydrogenase(GDH).Meanwhile,this crosstalk network could impede the efficacy of immunotherapy through mTORCI-P70S6K dependent PD-L1 production and PD-L1^(+)exosomes activity.In conclusion,our study highlights the non-coding regulatory role of HMGB1 with implicatio ns for RNA-based therapeutic targeting together with a predictio n of an ti-PD-L1 immuno therapy in HCC.展开更多
文摘By multiplexing information symbols in the delay-Doppler(DD)domain,orthogonal time frequency space(OTFS)is a promising candidate for future wireless communication in high-mobility scenarios.In addition to the superior communication performance,OTFS is also a natural choice for radar sensing since the primary parameters(range and velocity of targets)in radar signal processing can be inferred directly from the delay and Doppler shifts.Though there are several works on OTFS radar sensing,most of them consider the integer parameter estimation only,while the delay and Doppler shifts are usually fractional in the real world.In this paper,we propose a two-step method to estimate the fractional delay and Doppler shifts.We first perform the two-dimensional(2D)correlation between the received and transmitted DD domain symbols to obtain the integer parts of the parameters.Then a difference-based method is implemented to estimate the fractional parts of delay and Doppler indices.Meanwhile,we implement a target detection method based on a generalized likelihood ratio test since the number of potential targets in the sensing scenario is usually unknown.The simulation results show that the proposed method can obtain the delay and Doppler shifts accurately and get the number of sensing targets with a high detection probability.
基金This work was supported in part by the National Natural Science Foundation of China under Grant No. 61361166005, the National High Technology Research and Development Program of China under Grant No. 2014AA01A701, the National Basic Research Program of China （973 Program） under Grant No. 2013CB336600, and the State Major Science and Technology Special Projects （Grant No. 2016ZX03001020-006）.
基金supported by the National Key Research and Development Program of China(2017YFC1308900,2017YFC0908404,2018YFA0507503,2017YFA0505103)Beijing Municipal Government Key Research and Development Program(Z181100001918020,Z161100002616036)+4 种基金the National Natural Science Foundation of China(31870828,81972790,81672319)the Guangdong Provincial Key R&D Programmes(2019B020229002)the Science and Technology Program of Guangzhou(201902020009)the National Key Basic Research Program of China(2014CBA02002)the National Key Technology Support Program(2015BAI13B07).
文摘While precision medicine driven by genome sequencing has revolutionized cancer care,such as lung cancer,its impact on gastric cancer(GC)has been minimal.GC patients are routinely treated with chemotherapy,but only a fraction of them receive the clinical benefit.There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy.Here,we carried out retrospective analyses of 1,020 formalin-fixed,paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC.We identified two proteomic subtypes:the chemo-sensitive group(CSG)and the chemo-insensitive group(CIG)in the discovery set.The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only(64.2%vs.49.6%;Cox P-value=0.002),whereas no such improvement was observed in CIG(50.0%vs.58.6%;Cox P-value=0.495).We validated these results in an independent validation set.Further,differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC.A prospective study is warranted to test these findings for future GC patient care.
基金We gratefully acknowledge the support from the National Key R&D Program of China(2017YFA0504503)State Key Project on Infectious Diseases of China(2018ZX10723204-002-002)+2 种基金National Natural Science Foundation of China(91859205,81988101,81830054,81630070,81672777,81502416,and 82172896)Shanghai Rising-Star Program(17QA1405700)Shanghai Top Young Talents Program,Foundation of Shanghai Shenkang Hospital Development Center(SHDC2020CR2011A and SHDC12016127).
文摘Hepatocellular carcinoma(HCC)is the global leading cause of cancer-related deaths due to the deficiency of targets for precision therapy.A new modality of epigenetic regulation has emerged involving RNA-RNA crosstalk networks where two or more competing endogenous RNAs(ceRNAs)bind to the same microRNAs.However,the contribution of such mechanisms in HCC has not been well studied.Herein,potential HMGB1-driven RNA-RNA crosstalk networks were evaluated at different HCC stages,identifying the mT0RC2 component RICTOR as a potential HMGB1 ceRNA in HBV^(+)early stage HCC.Indeed,elevated HMGB1 mRNA was found to promote the expressio n of RICTOR mRNA through competitively bin ding with the miR-200 family,especially miR-429.Functio nal assays emplo ying overexpressi on or in terference strategies dem on strated that the HMGB1 and RICTOR 3zuntra nslated regions(UTR)epigenetically promoted the malignant proliferation,self-renewal,and tumorigenesis in HCC cells.Intriguingly,in terference agai nst HMGB1 and RICTOR in HCC cells promoted a stron ger an ti-PD-L1 immuno therapy resp on se,which appeared to associate with the production of PD-L1^(+)exosomes.Mechanistically,the HMGB1-driven RNA-RNA crosstalk network facilitated HCC cell glutamine metabolism via dual mechanisms,activating a positive feedback loop involving mT0RC2-AKT-C-MYC to upregulate glutamine synthetase(GS)expression,and inducing mTORCI signaling to derepress SIRT4 on glutamate dehydrogenase(GDH).Meanwhile,this crosstalk network could impede the efficacy of immunotherapy through mTORCI-P70S6K dependent PD-L1 production and PD-L1^(+)exosomes activity.In conclusion,our study highlights the non-coding regulatory role of HMGB1 with implicatio ns for RNA-based therapeutic targeting together with a predictio n of an ti-PD-L1 immuno therapy in HCC.
